American Society of Regional Anesthesia and Pain Medicine February 2018 - 29

methylprednisolone, with a biological half-life of 36-72 hours.11
Its potential to improve perioperative outcomes without significant
harm have been recognized in abdominal, orthopedic, and other
surgeries.20-22 As identified in the Cochrane review, despite the
potential for steroids to modify PPSP, overall, their effect on PPPS
has not been well studied.15
PROPOSAL
The PAIN-STOP pilot trial is a multicenter randomized controlled
trial (RCT) of 48 patients. This RCT will use a two-by-two
factorial design to evaluate NMDA antagonists versus placebo
and intravenous dexamethasone versus placebo. Patients will
be stratified based on site. Because the interventions work
through different biologic pathways, we do not expect a negative
interaction; hence, they are ideal drugs to study using a factorial
design in a single trial to increase the efficiency by capitalizing on
the resources required for an RCT.23 Patients, health care providers,
data collectors, outcome adjudicators, and investigators will all be
blind to treatment allocation. The study methods and outcomes are
highlighted in Table 1.
STRENGTHS
* The study focuses on an important and challenging question
that has been identified as a health priority.24
* The study interventions have sound biologic rationale and have
been identified as potentially promising for preventing PPSP.
More importantly, the interventions potentially cover the period
of transition from acute to chronic pain, as suggested by the
concept of preventive analgesia.7,25
* The factorial design allows for better efficiency in resources and
cost, allowing for assessment of two different interventions.
* The clinical outcomes satisfy the definition of PPSP by ICD-1126
and include clinically important, patient-relevant outcomes.
* The design is a multicenter, international study that
demonstrates the feasibility of a larger international trial with
the potential for greater clinical translation and applicability.
* The study team includes experienced and well-recognized
clinician investigators, research methodologists, and content
experts.
* The study is being coordinated from the Population Health
Research Institute at McMaster University in Hamilton, Canada,
which is recognized as a leading research institute engaged in
the conduct of large-scale, high-impact, randomized clinical
trials.
LIMITATIONS
* The timing, dose, and duration of study interventions have
been planned based on their biologic rationale and potential
for clinical applicability, as a pragmatic study. However, the
study will not be able to provide information on possible dosedependent effects or the impact of a different duration of study
interventions.

FUNDING
* 2016 Carl Koller Memorial Research Grant award, ASRA, in July
2016 with USD 50,624.20
* Michael G. DeGroote Institute of Pain Research and Care seed
grant, McMaster University, 2016 for CAD 30,000
REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT02950233?term=PAIn+STOP
&draw=1&rank=1
STUDY CHALLENGES
* Acquisition of memantine tablets at 5-mg and 10-mg strengths
from a licensed supplier
* Obtaining approval of health regulatory authorities
* Collaborating and coordinating interdepartmental involvement
(anesthesiologists, surgeons, pharmacy, nursing, clinical
research) for the smooth conduct of the trial.
STUDY UPDATES
As of September 2017, the following updates indicate the study
progress.
* The study has obtained approval of health regulatory authorities
(Health Canada and the US Food and Drug Administration) for
the use of investigational drugs.
* The study's memantine and placebo medications were
encapsulated, labeled, and packaged.
* After approval from the ethics board, the study has been
initiated at McMaster University in Hamilton, Canada, since May
2017.
* An ethics committee application at Cleveland Clinic will be
submitted in October 2017.
* Ten patients have been recruited and completed their surgery.
* The study started at Cleveland Clinic in November 2017.
* Recruitment will be completed by April 2018 and follow-up
completed by July 2018.
ACKNOWLEDGMENTS
I would like to acknowledge the support from our funding agencies
and the entire PAIN-STOP investigating team.
REFERENCES
1.

Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and
prevention. Lancet 2006;367(9522):1618-1625.

2.

Wildgaard K, Ravn J, Kehlet H. Chronic post-thoracotomy pain: a critical review
of pathogenic mechanisms and strategies for prevention. Eur J Cardiothorac
Surg 2009;36(1):170-180.

3.

Gottschalk A, Cohen SP, Yang S, Ochroch EA. Preventing and treating pain after
thoracic surgery. Anesthesiology 2006;104(3):594-600.

4.

Gureje O, Von Korff M, Simon GE, Gater R. Persistent pain and well-being: a
World Health Organization Study in Primary Care. JAMA 1998;280(2):147-151.

5.

Woolf CJ. Central sensitization: implications for the diagnosis and treatment of
pain. Pain 2011;152(3 suppl):S2-S15.

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2018

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https://www.clinicaltrials.gov/ct2/show/NCT02950233?term=PAIn+STOP&draw=1&rank=1 https://www.clinicaltrials.gov/ct2/show/NCT02950233?term=PAIn+STOP&draw=1&rank=1

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